The overall goal of this proposed research is to investigate the control of peripheral vascular resistance in conscious neonatal lambs. The studies include 1) the definition of dose response relationships of phenylephrine (representative of alpha1- adrenergic stimulation), angiotensin II and vasopressin infused into the hind limbs of newborn lambs to femoral arterial blood flow in that limb; 2) the development of the model of local receptor blockade in the hind limb of the newborn lamb, focusing on the alpha1, vasopressin (V1) and angiotensin II receptors; 3) the determination of the hemodynamic and endocrine changes that occur in lambs in response to different degrees of blood loss; 4) the evaluation of the relative roles of receptors in the development of vascular resistance during hemorrhage by bleeding the animals during regional blockade. Chronically cannulated newborn lambs are chosen for the project because it is possible to study the cardiovascular and endocrine relationships in these animals in the absence of the physiologic changes brought about by surgery and anesthesia. The research will further knowledge on the control of peripheral vascular resistance by endocrine reflexes. Hypotension of various causes is a frequent clinical problem facing human newborns. Increased understanding of the adaptive mechanisms used by neonates in response to hypotension may prove important in the development of management strategies for the premature infant or the term infant with hypotension.